New Paper led by Ole Kemi
Published: 19 September 2023
Paper by SCMH Members
Electrically stimulated in vitro heart cell mimic of acute exercise reveals novel immediate cellular responses to exercise: Reduced contractility and metabolism, but maintained calcium cycling and increased myofilament calcium sensitivity
Ana Da Silva Costa, Iffath Ghouri, Alexander Johnston, Karen McGlynn, Andrew McNair, Peter Bowman, Natasha Malik, Johanne Hurren, Tomas Bingelis, Michael Dunne, Godfrey L. Smith, Ole J. Kemi
Summary
We know that endurance exercise is taxing to the heart and it leads to cardiac exhaustion and fatigue with contractile impairment. However, what we don’t know is a mechanism for this, and this is at least partly because this has been impossible to study in heart muscle cells (cardiomyocytes, the cells that make contraction happen), since the process of ascertaining and isolating cells for study after physical exercise in and of itself uncouples, or kills if you like, the exercise effect. In this study, the scientists and authors of this newly published paper took a different approach and came up with a novel protocol; instead of exercising animals and then preparing cells, like one would traditionally have done, the scientists first prepared cells, made sure they were well-prepared and rested in physiologic steady-state conditions and only then exercised the cells. Exercise for the heart is essentially a bout of repeated high-frequency electrical stimulations (exercise at high heart rate) for as long as the exercise lasts, so this was re-produced and the cells stimulated with high-frequency electrical stimulation protocols that mimicked “real” exercise, all in a cell chamber that ensured cells were adequately perfused with nutrients, oxygen and physiologic solution and mounted onto an advanced imaging fluorescence and video microscope. After optimizing the protocols to make them as close to real endurance exercise as possible, the results then showed that exercise gradually lead to a reduction in cell and myofilament contractile function, and that this was caused by acidosis (low pH) and metabolic impairments that resulted in not enough adenosine triphosphate (ATP) being generated by the mitochondria (shown by autofluorescence measurements of redox function), which is a problem since contractions demand a high amount of energy in the form of ATP that needs to be continually generated in the mitochondria. On the other hand, intracellular calcium, another cell mechanism for contraction, was not impaired during the exercise lessened and in fact worked to lessen the contractile dysfunction, by sustaining normal cellular calcium release and also increasing the myofilament sensitivity to calcium, presumably in order to alleviate the dys-contraction effect. Therefore, we now know a bit more about what happens in the heart when we exercise, at a very fundamental cellular and sub-cellular level.
Senior author Dr Ole Kemi also adds, “this was a pretty big effort over a long period of time and one that involved many former students at both undergraduate and postgraduate levels, some of which have moved on to staff roles in SCMH and MVLS, as well as academic and technical staff that are still present at SCMH. A big thank you to all.”
First published: 19 September 2023